1. Field of the Invention
This invention relates to human conglutinin, polyclonal and monoclonal anti-conglutinin antibody raised against human conglutinin, and their uses in therapy and diagnosis.
2. Description of Background Art
Conglutinin is the name given by Bordet and Streng (Zentr.Bakteriol.Parasitenk. Abt. 1 Orig. 49 (1909) pp. 260-276) to the component in bovine serum which induce the agglutination of erythrocytes coated with antibody and complement. Conglutinin was quite extensively studied at the beginning of this century and later reinvestigated by Coombs et al.: "The Serology of Conglutination and its Relation to Disease" (1961) Blackwell, Oxford, and Lachmann: Adv.Immunol. 6 (1967) pp. 479-527.
The activity was ascribed to a large, elongated protein molecule (Sage et al. J.Immunol. 90 (1963) pp. 347-357). More specifically, conglutinin was found to induce agglutination of erythrocytes exposing the C3 degradation product, iC3b. The C3b inactivating factor (Factor I) which splits the .alpha.-chain of C3b was thus originally named conglutinogen activation factor (or KAF) (Lachmann and Muller-Eberhard, J.Immunol. 100 (1968) pp. 691-698). Apparently, conglutinin shows no reactivity with native C3 or the further degraded fragments, C3dg or C3c. This has, however, lately been questioned since solid phase conglutinin in enzyme linked immunosorbent assays (ELISA) has been found to bind fluid phase C3c and C3b as well as iC3b (Hirani et al., J.Immunol. 134 (1985) pp. 1105-1109).
The physiological function of conglutinin remains hitherto unknown. Studies in bovidae have revealed that the content of conglutinin in blood decreases during infection and at parturition (Ingram D. G. "Biological aspects of conglutinin and immunoconglutinins, pp. 215-228 in D. A. Ingram Ed. "Biological Activities of Complement" Karger, Basel, Switzerland).
Conglutinin shows protective activity against bacterial infections as shown by Ingram D.G. (Immunology 2, 322-333, 1959 and Immunology 2, 334-345, 1959) in experiments where mice could be protected by the injection of bovine conglutinin in the form of a euglobulin precipitate from normal bovine serum redissolved in saline before the injection of pathogenic bacteria. This indicates that conglutinin is of importance for the non-specific immunity.
Conglutinin's binding of complement solubilized immune complexes has attracted interest. Immune complex assays based on this activity are popular and solid phase bovine conglutinin has been used to purify soluble circulating immune complexes (Casali and Lambert, Clin.Exp.Immunol. 37 (1979) pp. 295-309).
Conglutinin may be classified as a lectin on the basis of its reactivity with carbohydrates.
Attempts at demonstrating conglutinin in other species than the bovidae has generally failed (Davis and Lachmann, Biochemistry 23 (1984) p. 2139). However, some authors have claimed indications for the existence of conglutinin in swine (Barta et al., J.Immunol. 105 (1970) p. 350), and in sheep (Jonas and Stankiewiecz, Veterinary Immunology and Immunopathology 5 (1983/84 p. 289).
Despite considerable efforts the only possible analogue in the human so far described is the iC3b receptor (CR3) (Ross et al., J.Immunol. 134 (1985) pp. 3307-3315), which shows no structural homology to bovine conglutinin.
By employing functional and immunochemical analysis the inventors have now succeeded in isolating, demonstrating and characterizing human conglutinin.